Continuing advancements in medicine have increased the use of synthetic materials that come into direct contact with blood and other physiological fluids. Synthetic materials have been used in many areas of medical treatment including artificial ocular lenses, heart valves, bypass tubes, implants, shunts, dialysis machines, catheters and other blood and fluid contacting devices or apparatus. Although the synthetic materials used to manufacture medical devices are mechanically stable and chemically inert, these synthetic materials are generally not biocompatible when exposed to bodily fluids such as blood.
Biocompatibility involves a number of parameters related to how the medical device interacts with the host. Undesirable physiological reactions such as thrombosis, which is the formation of blood clots, or bacterial infection may result because the synthetic materials of which medical devices are manufactured cause proteins and other physiological fluid components to adhere to their surfaces. The more prolonged the contact, the more likely infection and thrombosis will occur.
Thrombosis is the body's natural mechanism to prevent uncontrollable bleeding whenever the lining of the vasculature is disturbed. The introduction of medical devices sometimes initiates this natural defense mechanism. In addition, the synthetic surface of many medical devices may exacerbate the thrombogenic response. A thrombus, or a portion of a thrombus, may break free and travel throughout the vascular system, potentially causing serious problems downstream.
Substantial research and development has been undertaken to control, if not eliminate, infection and thrombogenesis caused by medical devices. The vast majority of metals and synthetic polymers used to manufacture medical devices do not have antimicrobial or antithrombogenic capabilities of their own. Consequently, most measures undertaken for creating antimicrobial and antithrombogenic devices involve either the addition of some component or the application of a covering to the synthetic material of the medical device. For example, a common precaution to prevent thrombus formation is to treat the medical device surface with an anticoagulant substance such as heparin or with heparin reacted with a quaternary ammonium compound. Heparin interferes with the coagulation cascade, thereby inhibiting thrombus formation.
Certain oligodynamic metals, such as silver, are well known to have an antiseptic action, and have been mixed with a dissimilar noble metal, such as platinum, and embedded in a polymer that is loaded with a conductive material such as carbon black. When this polymer comes into contact with the electrolytic bodily fluids of a patient, a galvanic current flow is produced through the conductive material between the two metals, causing ions of the oligodynamic metal to be released into the body. For example, the silver acts as a sacrificial electrode in the circuit giving off silver ions that are bacteriostatic and can stop the growth of bacteria on the surface of the medical device. Medical devices incorporating this technology are shown and described in WO 97/38648, and materials made thereby are termed iontophoretic.
Plasticized polymers, such as polyvinyl chloride (PVC), are common for use in tubing for various medical machines and devices, such as heart and lung machines and dialysis machines, and in the manufacture of catheters, due to desirable attributes such as greater flexibility and tensile strength. Loading a polymeric material with high levels of a conductive material, such as carbon black, to complete a galvanic circuit between embedded oligodynamic and noble metals is not possible for highly plasticized polymers, since a large percentage of the material is the nonconductive, oily plasticizer. The carbon black particles must be loaded at such high concentrations that they physically touch, which would change the entire nature of the plasticized polymer and decrease or eliminate many of its desired attributes.
In summary, there are several previously disclosed antimicrobial, antithrombogenic and combined antimicrobial/antithrombogenic coatings for medical devices. While these coatings achieve the desired effect of preventing blood clot formation, or thrombogenesis, and infection from insertion and use of the medical device within the human body, each of the disclosed methods has various limitations.